Identification of a 55-bp deletion in the glucocerebrosidase gene in Gaucher disease: phenotypic presentation and implications for mutation detection assays.

A 55-bp deletion in exon 9 of the glucocerebrosidase gene was identified in a 28-year-old male affected with Gaucher disease. The diagnosis was established during an evaluation for mild pancytopenia and was confirmed by bone marrow histology and biochemical studies. The patient is of German ancestry. Initial DNA testing indicated homozygosity for the N370S mutation. However, subsequent testing of the patient's parents suggested that the patient and his mother carried a null allele by our assay for N370S. Further molecular studies identified a 55-bp deletion in exon 9 of the glucocerebrosidase gene (g.6767_6822del55). This deletion has been previously reported in a patient with severe Gaucher disease (1), and is present in the glucocerebrosidase pseudogene. In the previously reported case, initial DNA testing also suggested the genotype N370S/N370S, but further mutation studies were undertaken because clinical severity was greater than expected for that genotype. In contrast, our patient has an unusually mild clinical course. Thus, clinical severity cannot be reliably used to determine when to test for the presence of the 55-bp deletion. While the 55-bp deletion is not reported to be common, its actual frequency may be underestimated since it eludes detection by many standard clinical assays for Gaucher disease. This report points out the need to consider this deletion mutation which may cause erroneous interpretation of results in existing assays for the common mutations N370S and L444P. Furthermore, the importance of recommending parental analysis for individuals who test homozygous for autosomal mutations is highlighted.